Matrix metalloproteinases and their inhibitors and inducer in gestational trophoblastic diseases and normal placenta

ObjectivesThis study aimed to investigate the expression of recently identified matrix metalloproteinases (MMPs), their inhibitors (TIMPs), and inducer (CD147) in a wide range of gestational trophoblastic diseases (GTD) thereby expanding our understanding of the potential role of MMPs in GTD.MethodsParaffin sections of 10 normal first-trimester placentas (NP), 10 partial moles (PM), 10 complete moles (CM), 5 choriocarcinomas (CCA) and 5 placental site trophoblastic tumors (PSTT) were studied immunohistochemically for expression of MMP-7, MMP-14, MMP-21, MMP-28, TIMP-3, TIMP-4 and CD147. Immunolocalization of MMP-1, MMP-2, MMP-3, MMP-9, MMP-13 and TIMP-1 was performed on 5 CCA and 5 PSTTs.ResultsCCA showed stronger intensity for MMP-14 and MMP-28 than PSTT (p < 0.05, p < 0.05). CCA and PSTT had stronger expression of MMP-21 than NP, PM and CM (p < 0.05, p < 0.05, p < 0.01). PSTT (p < 0.05, p < 0.05), NP (p < 0.01, p < 0.01) and CM (p < 0.01, p < 0.05) showed stronger staining for TIMP-3 and TIMP-4 than CCA.ConclusionChoriocarcinoma's high expression of MMPs and low expression of MMP inhibitors may contribute to its invasiveness and metastatic potential. Similarly, PSTT's lower expression of MMPs and high expression of MMP inhibitors may partly explain its lower invasiveness. Agents that inhibit MMP may prove useful in treating GTD.

Research Highlights
► Expands our understanding of MMPs in gestational trophoblastic disease.
► May help explain the biologic behavior of different types of gestational trophoblastic disease.
► Important in developing novel treatment for drug resistant trophoblastic disease.